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Trasplante Renal |
Bibliografia |
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TRAS-ALERTTransplantation 1998 Nov 15;66(9):1254-8
Hepatitis C virus-associated fibrosing cholestatic hepatitis after renal
transplantation: response to interferon-alpha therapy.
Toth CM, Pascual M, Chung RT, Graeme-Cook F, Dienstag JL, Bhan AK, Cosimi AB
Transplantation Unit, Massachusetts General Hospital, and Harvard Medical School, Boston
02114, USA.
Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ
transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is
characterized by an ominous clinical course leading to progressive hepatic failure and
death if liver transplantation is not performed. Two HCV-infected patients underwent
cadaveric renal transplantation for end-stage renal disease resulting from membranous
nephropathy and diabetic nephropathy. The time intervals between transplantation and the
biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients
presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum
aspartate aminotransferase. One patient was also found to have type II mixed
cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was
established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic
hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis
of FCH should be considered and a liver biopsy performed. Our observations indicate that
FCH can respond to antiviral therapy.
PMID: 9825826, UI: 99041173
Transplantation 1998 Nov 15;66(9):1238-43
Role of donor and recipient antigen-presenting cells in priming and maintaining T
cells with indirect allospecificity.
Frasca L, Amendola A, Hornick P, Brookes P, Aichinger G, Marelli-Berg F, Lechler RI,
Lombardi G
Department of Immunology, ICSM, Hammersmith Hospital, London, United Kingdom.
BACKGROUND: It has been suggested that the sensitization of recipient T lymphocytes
against peptides derived from allogeneic major histocompatibility complex (MHC) antigens
in the context of self-MHC molecules may contribute to the pathogenesis of chronic
allograft rejection. The purpose of this study was to quantitate and characterize the
indirect alloresponse in renal transplantation. METHODS: An HLA-A2-negative patient whose
A2-positive kidney transplant failed as a result of chronic rejection was selected for
this study. T-cell clones were raised using a cocktail of peptides corresponding to
polymorphic regions of the A2 sequence and studied by measuring their proliferation using
[3H]thymidine incorporation. The presence in vivo of HLA-A2-specific T cells was assessed
using limiting dilution analysis. RESULTS: T-cell clones were specific for a single
peptide of HLA-A2, residues 92-120, and restricted by HLA-DRB1*1502. The frequency of
interleukin-2-secreting T cells specific for this A2 peptide was 1:86,000, only 2-fold
lower than that measured against the recall antigen tetanus toxoid. Capitalizing on the
similarity of the donor and recipient DR15 alleles (DRB1*1501 and 1502), the question was
addressed as to how these T cells had been primed in vivo. Although the large majority of
clones responded to A2 synthetic peptide presented by both DR15 alleles, only 3 of 10
clones responded to cells co-expressing DRB1*1501 and A2. CONCLUSION: These data suggest
that antigen presentation by recipient APCs is responsible for maintaining T cells with
indirect allospecificity in vivo and that, in the context of partial DR matching, indirect
presentation by the parenchymal cells of the graft may serve to induce tolerance in T
cells with indirect allospecificity.
PMID: 9825823, UI: 99041170
Transplantation 1998 Nov 15;66(9):1207-10
Steroid-free immunosuppression after kidney transplantation with antithymocyte
globulin induction and cyclosporine and mycophenolate mofetil maintenance therapy.
Birkeland SA
Department of Nephrology, Odense University, Denmark. S.A.Birkeland@OUH.DK
BACKGROUND: Our goal in clinical renal transplantation is to find immunosuppressive
procedures that not only promote long-term patient and graft survival but also improve the
overall well-being of the patients. METHODS: In a retrospective consecutive clinical study
with historical controls, 68 patients were discharged from our center with functioning
grafts between September 1995 and December 1997. Patients received steroid-free
immunosuppression using an initial 10-day antithymocyte globulin induction and maintenance
therapy with cyclosporine and mycophenolate mofetil (MMF). No steroids were given.
RESULTS: After an observation for up to 2.5 years (median 488 days, range 127 to 945
days), 66 patients (one died from sepsis after 6 months, and one died of peritonitis after
returning to dialysis) were alive and well. Sixty-four grafts were functioning well,
hemolytic uremic syndrome recurred in one graft, one graft had to be removed for
noncompliance, and two patients returned to dialysis after chronic rejection-one after 8
months (the patient who died in peritoneal dialysis) and one (a third graft in an
antibody-positive patient) 16 months after transplantation. We observed only 10 acute
rejections (15%), a rate significantly lower (P=0.0006) than the 71 acute rejections
observed in 190 previous consecutive transplants (37.4%) treated without MMF but otherwise
after exactly the same protocol. In further comparison, the MMF-treated group also showed
an equivalent (P=NS) rate of cytomegalovirus infections and a lower rate (P<0.00005) of
Epstein-Barr virus infections. Graft function was excellent (median serum creatinine below
200 micromol/L at 1 year), and no malignancies were observed in the MMF-treated patients.
Side effects were mainly leukopenia and two gastrointestinal disturbances. CONCLUSIONS:
Our first-line, steroid-free immunosuppressive protocol allows initial graft function,
provides a safe level of long-term graft survival and function with a very low rejection
rate, gives an acceptable rate of side effects, and possesses the potential for lowering
the incidence of chronic rejection over the long-term. Compared with protocols that
discontinue steroids after the initial posttransplant period, a steroid-free protocol
avoids the increased risk of infection and body disfigurement in the early posttransplant
period. It also avoids the long-term risks of steroid use and the increased risks of
rejection when the steroids are withdrawn.
PMID: 9825819, UI: 99041166
Transplantation 1998 Nov 15;66(9):1186-92
Long-term outcome of a prospective randomized trial of conversion from
cyclosporine to azathioprine treatment one year after renal transplantation.
MacPhee IA, Bradley JA, Briggs JD, Junor BJ, MacPherson SG, McMillan MA, Rodger RS, Watson
MA
Renal Transplant Unit, Western Infirmary, Glasgow, Scotland.
BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival
has improved, but concern persists about the long-term adverse effects of CsA, especially
with respect to renal function and blood pressure. This randomized controlled trial was
set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS:
Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine
of less than 300 micromol/L and who had not had acute rejection within the last 6 months
were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to
stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone.
Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS:
There was no significant difference in actuarial 10-year patient or graft survival
(Kaplan-Meier), despite an increased incidence of acute rejection within the first few
months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119
micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement
for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients
required antihypertensive treatment at the start of the study, decreasing to 55% from 1
year after randomization in the Aza group and increasing to >80% in the CsA group (55%
(Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion
from CsA to Aza at 1 year after renal transplantation results in improvement in both blood
pressure control and renal allograft function, and is not associated with significant
adverse effects on long-term patient or graft survival.
PMID: 9825816, UI: 99041163
Transplantation 1998 Nov 15;66(9):1159-63
Renal transplantation with limit donors: to what should the good results obtained
be attributed?
Sola R, Guirado L, Lopez Navidad A, Caballero F, Agraz I, Diaz M, Paredes D, Rodrigez S,
Vizcarra D
Kidney Transplant Unit, Nephrology Service, Fundacio Puigvert, Barcelona, Spain.
BACKGROUND: With the aim of offsetting the reduction in donors of kidneys for
transplantation, we extended the acceptance criteria, considering donors over 60 years
old. METHODS: The results obtained in 84 transplants carried out with this type of donor
(group A) was compared with those of a control group of 125 transplants carried out with
kidneys from donors under 60 years old (group B). The protocol for selection of donors was
appropriate creatinine clearance, minimum proteinuria, and normal renal scan. The
histological study was not included because it was not considered appropriate to assess
the extent of the possible glomerulosclerosis, as this has a focal, segmented
distribution. There were no significant differences between the recipients except for age
(57.8 years old in group A vs. 39.2 years in group B). RESULTS: After the transplantation,
there were significant differences in the duration of hospitalization (26.8 days vs. 21.8
days, P<0.009), annual plasma creatinemia (177, 225, 233, 235, and 205 micromol/L vs.
136, 150, 121, 111, and 133 micromol/L, P<0.0002/0.0004), graft survival (87%, 85%,
81%, 81%, and 81% vs. 89%, 88%, 86%, 86%, and 85%, P<0.03), and patient survival (92%,
89%, 85%, 85%, and 85% vs. 99%, 99%, 97%, 96%, and 95%, P<0.0004). Death of the patient
was the only significantly more frequent cause of graft loss among group A patients (7 vs.
1 death, P<0.004). No kidney was "never working" and none were lost because
of chronic rejection. CONCLUSIONS: It was concluded that elderly donors should be
considered as suitable for transplantation irrespective of their chronological age,
provided that they fulfill the acceptance criteria. The quality of life achieved was
comparable in both groups. Despite the lower renal function in group A, this remained
constant during the follow-up period.
PMID: 9825811, UI: 99041158
Am J Kidney Dis 1998 Nov;32(5):820-4
Cytomegalovirus-induced necrotizing and crescentic glomerulonephritis in a renal
transplant patient.
Detwiler RK, Singh HK, Bolin P Jr, Jennette JC
Department of Pathology, East Carolina University School of Medicine, Greenville, NC
27858, USA. rdetwiler@ccusom.som
A 35-year-old black man with end-stage renal disease from biopsy-proven focal segmental
glomerulosclerosis developed worsening function of his renal allograft 160 days after
living related donor renal transplantation. Renal biopsy showed necrotizing and crescentic
glomerulonephritis (NCGN) and presence of intraglomerular viral inclusions confirmed by
immunocytochemical stain and in situ hybridization techniques to be cytomegaloviral in
origin. Electron microscopy showed no immune complexes, and workup for other causes of
NCGN was negative. The patient was treated with ganciclovir withoutother changes in his
immunosuppressive regimen. After 8 weeks of ganciclovir therapy, a second renal transplant
biopsy showed resolution of the glomerular process and disappearance of the
cytomegalovirus (CMV) inclusions. The resolution of the glomerular process with treatment
for CMV infection, and without other change in therapy, strongly supports a causative link
between CMV and NCGN in this patient. This case represents the first report of
CMV-associated NCGN in a renal transplant patient.
PMID: 9820453, UI: 99036339
Am J Kidney Dis 1998 Nov;32(5):813-9
Effective treatment of high-grade lymphoproliferative disorder after renal
transplantation using autologous lymphocyte activated killer cell therapy.
Li PK, Tsang K, Szeto CC, Wong TY, To KF, Leung CB, Lui SF, Yu S, Lai FM
Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin.
philipli@cuhk.edu.hk
Posttransplantation lymphoproliferative disorders (PTLD) is not uncommon and can occur in
2% to 5% of solid organ recipients on immunosuppression. Epstein-Barr virus (EBV)
infection or reactivation and intensive anti-T lymphocyte treatment are important
pathogenetic factors for a large proportion of these disorders. Nonclonal lesions with
polymorphous histology have a potential for regressing when the immunosuppressants are
reduced or stopped. Clonal tumors with a monomorphous histology carry a poor prognosis,
and the mortality rate for monoclonal lymphoma has been reported as high as 80%. We report
a renal transplant recipient who developed high-grade monoclonal lymphoma only 4 months
after a live-donor transplantation. The tumor was EBV positive. Reduction of
immunosuppressants resulted in minimal regression of the tumor. The patient was treated
with adoptive immunotherapy using ex vivo generation of autologous lymphocyte activated
killer (LAK) cells. She had leukapheresis, and autologous peripheral blood mononuclear
cells were obtained and cultured in interleukin-2 (IL-2)-rich medium for 9 to 10 days. The
IL-2-activated LAK cells were reinfused into the patient without any systemic
administration of IL-2. The patient experienced no side effects during the infusion. There
was no rejection episode, and the renal function of the patient remained stable after
treatment. Computed tomography scan performed 2 months after the infusion showed marked
regression of the lesions in the liver and spleen. Five months later, magnetic resonance
imaging showed complete resolution of the tumor lesions. Ultrasonography 13 months after
the LAK cell infusion showed no lesion. The allograft function was not affected after
treatment. Adoptive immunotherapy using IL-2-activated autologous LAK cells was effective
in treating this renal transplant patient with EBV-positive high-grade lymphoma. The
patient's kidney allograft functioned well without any rejection.
PMID: 9820452, UI: 99036338
J Inherit Metab Dis 1998 Oct;21(7):729-37
Renal transplantation in a patient with methylmalonic acidaemia.
Van Calcar SC, Harding CO, Lyne P, Hogan K, Banerjee R, Sollinger H, Rieselbach RE, Wolff
JA
Waisman Center, University of Wisconsin-Madison, USA.
Renal insufficiency is frequently reported in mutase-deficient methylmalonic acidaemia. We
present a case report of a patient with mut- methylmalonic acidaemia who developed chronic
tubulointerstitial nephropathy during adolescence. At 24 years of age, she developed
end-stage renal failure and underwent renal transplantation. Both plasma and urine
methylmalonic acid levels decreased significantly with improved renal function following
transplantation. Complications included cyclosporin toxicity and development of diabetes.
Renal, metabolic, and clinical status remained improved at 3 years after the kidney
transplant.
PMID: 9819702, UI: 99037137
J Urol 1998 Dec;160(6 Pt 1):1982-5; discussion 1985-6
A prospective, randomized trial to compare tacrolimus and prednisone with and
without mycophenolate mofetil in patients undergoing renal transplantation: first report.
Shapiro R, Jordan ML, Scantlebury VP, Vivas C, Gritsch HA, Casavilla FA, McCauley J,
Johnston JR, Randhawa
P, Irish W, Hakala TR, Fung JJ, Starzl TE
Thomas E. Starzl Transplantation Institute, Department of Medicine, University of
Pittsburgh, Pennsylvania, USA.
PURPOSE: Between September 20, 1995 and September 20, 1996, 120 patients were entered into
a prospective, randomized trial comparing tacrolimus and prednisone with (61) and without
(59) 2 gm. mycophenolate mofetil daily to determine whether mycophenolate mofetil was
associated with a lower incidence of rejection. MATERIALS AND METHODS: Mean recipient age
plus or minus standard deviation was 50.8+/-14.1 years (range 18.8 to 84.1). Mean donor
age was 34.3+/-21.7 years (range 0.01 to 76). Of the donors 18 (15%) were older than 60
years. Mean cold ischemia time was 30.9+/-8.4 hours (range 14.2 to 49). Median followup
was 8.6+/-0.5 months. RESULTS: The 6-month actuarial patient survival was 95%, 92% in the
double therapy group and 98% in the triple therapy group (not significant). The 6-month
actuarial graft survival was 88%, 84% in the double therapy group and 92% in the triple
therapy group (not significant). The overall incidence of rejection and steroid resistant
rejection was 34.2 and 4.2%, respectively. There was a strong trend toward less rejection
in the mycophenolate mofetil group than in the double therapy group (26.2 versus 42.4%).
Crossover was common, and was 42.6% from triple to double therapy and 18.6% from double to
triple therapy. The reasons for discontinuation of mycophenolate mofetil were
gastrointestinal toxicity, primarily diarrhea, or less commonly hematological toxicity,
primarily neutropenia or thrombocytopenia. Gastrointestinal toxicity was ameliorated by
separating the doses oftacrolimus and mycophenolate mofetil by 2 to 4 hours, and reducing
the dose to 1 gm. daily. CONCLUSIONS: Mycophenolate mofetil appears to be a useful third
agent with tacrolimus in patients undergoing renal transplantation, and is associated with
a reduction in the rate of rejection and a low incidence of steroid resistant rejection.
There is a high incidence of gastrointestinal toxicity associated with the 2 gm. daily
dose but this complication is relatively straightforward to manage.
PMID: 9817305, UI: 99032217
Pediatr Nephrol 1998 Oct;12(8):666-7
Ureteral urine leak presenting as a pleural effusion in a renal transplant
recipient.
Kees-Folts D, Cole BR
Department of Pediatrics, The Milton S. Hershey Medical Center of the Penn State Geisinger
Health System, Hershey,
Pennsylvania 17033, USA.
We report a 15-year-old girl who developed a ureteral perforation soon after
living-related donor renal transplantation. Her presentation was unusual in that a
symptomatic pleural effusion accumulated as an extension of the perinephric urine
collection. Recognition and surgical correction of the ureteral pathology led to
resolution of respiratory symptomatology and full recovery of renal function.
PMID: 9811392, UI: 99027531
Transplantation 1998 Oct 27;66(8):1053-8
Erythrocytosis after renal transplantation represents an abnormality of
insulin-like growth factor-I and its binding proteins.
Brox AG, Mangel J, Hanley JA, St Louis G, Mongrain S, Gagnon RF
Division of Hematology, Royal Victoria Hospital, McGill University, Montreal, Quebec,
Canada.
BACKGROUND: Secondary erythrocytosis is classically defined by an increase in
erythropoietin (EPO) production. Despite increased levels of EPO often seen in secondary
erythrocytosis, some of these forms such as that seen after renal transplantation remain
undefined. Our group has recently investigated the in vivo function of insulin-like growth
factor-I (IGF-I) in erythropoiesis both in humans and in a murine model of chronic renal
failure. These data, and the recently recognized role of IGF-I in polycythemia vera,
suggested that IGF-I might be involved in secondary erythrocytosis. METHODS: Renal
transplant recipients who developed erythrocytosis after transplantation were compared to
normal individuals and to renal transplant recipients without erythrocytosis. We measured
fasting serum EPO and IGF-I in all three groups. Because binding proteins may modify IGF-I
function, IGF-I-binding proteins (IGFBP) 1 and 3, major binding proteins of IGF-I, were
also measured. RESULTS: Renal transplant recipients have significantly elevated serum of
IGF-I and IGFBP3 compared to normal individuals. When transplant recipients with and
without posttransplant erythrocytosis were compared, similar levels of IGF-I were found;
however, the group with erythrocytosis had significantly elevated IGFBP1 and IGFBP3. No
other significant differences including EPO levels were found between the groups.
CONCLUSIONS: Erythrocytosis after renal transplantation represents an anomaly of both
IGF-I and its major binding proteins. Further studies are under way to better define this
dysregulation and determine whether IGF-I can play a more generalized role in secondary
forms of erythropoiesis.
PMID: 9808491, UI: 99023677
Transplantation 1998 Oct 27;66(8):1040-6
Immunosuppressive effects and safety of a sirolimus/cyclosporine combination
regimen for renal transplantation.
Kahan BD, Podbielski J, Napoli KL, Katz SM, Meier-Kriesche HU, Van Buren CT
Department of Surgery, The University of Texas Medical School at Houston, 77030, USA.
BACKGROUND: Sirolimus, a novel immunosuppressant that inhibits cytokine-driven cell
proliferation and maturation, prolongs allograft survival in animal models. After a phase
I trial in stable renal transplant recipients documented that cyclosporine and sirolimus
have few overlapping toxicities, we conducted an open-label, single-center, phase I/II
dose-escalation trial to examine the safety and efficacy of this drug combination.
METHODS: Forty mismatched living-donor renal transplant recipients were sequentially
assigned to receive escalating initial doses of sirolimus (0.5-7.0 mg/m2/day), in addition
to courses of prednisone and a concentration-controlled regimen of cyclosporine. We
conducted surveillance for drug-induced side effects among sirolimus-treated patients and
compared their incidence of acute rejection episodes as well as mean laboratory values
with those of a historical cohort of 65 consecutive, immediately precedent,
demographically similar recipients treated with the same concentration-controlled regimen
of cyclosporine and tapering doses of prednisone. RESULTS: The addition of sirolimus
reduced the overall incidence of acute allograft rejection episodes to 7.5% from 32% in
the immediately precedent cyclosporine/prednisone-treated patients. At 18- to 47-month
follow-up periods, both treatment groups displayed similar rates of patient and graft
survival, as well as morbid complications. Although sirolimus-treated patients displayed
comparatively lower platelet and white blood cell counts and higher levels of serum
cholesterol and triglycerides, sirolimus did not augment the nephrotoxic or hypertensive
proclivities of cyclosporine. The degree of change in the laboratory values was more
directly associated with whole blood trough drug concentrations than with doses of
sirolimus. CONCLUSIONS: Sirolimus potentiates the immunosuppressive effects of a
cyclosporine-based regimen by reducing the rate of acute rejection episodes.
PMID: 9808489, UI: 99023675
J Am Soc Nephrol 1998 Nov;9(11):2148-52
Living unrelated renal transplantation: progress and potential.
Said MR, Curtis JJ
Division of Nephrology, University of Alabama at Birmingham, 35295-0007, USA.
Transplant centers are turning to emotionally related or living unrelated kidney donors
more often than in the past. Such donors are a benefit to the patient with end-stage renal
disease, yet concern about their use persists. In the United States, the use of related
donors has been well established in most centers. Nonetheless, there had been a reluctance
to use nonrelatives that only recently has started to change. Most physicians agree that
kidney transplant results are improved with living unrelated donor utilization. The
transplant community needs to be watchful of the living unrelated donor operation. Both
the welfare of the donor and the possibility of a "slippery slope" toward kidney
bartering are considerations that need careful monitoring.
PMID: 9808104, UI: 99023290